Menopause results in the dramatic decline of estrogen and progesterone. Converging evidence suggestive that low estrogen replacement therapy (ERT). ERT seems to improve memory in many older women. However, these studies are confounded by several factors. Also, effects of progesterone on cognition in older women have been virtually ignored, though it declines in parallel with estrogen. Many studies suggest that cortisol, another steroid, also influences cognition during aging. Together, variations in these hormones may help explain much of the individual variation in age-related cognitive decline. No studies have correlated endogenous estrogen, progesterone, or cortisol levels in post-menopausal women with objective cognitive performance. Here, levels of estrogen, progesterone, and cortisol will be measured in healthy older women participating in another longitudinal study of cognition. Cognitive status of the subjects ranges from youthful, control levels to mild dementia. The proposed work will compare endogenous hormone levels with contemporaneous cognition and longitudinal cognitive profile over the preceding 4 years. Women on ERT will be compared with women not taking estrogen supplements. Interaction of the hormones in their relationship to cognition will also be examined. This work will help establish the levels of estrogen associated with optimal memory maintenance and/or protection from age-related memory problems in women. Oral ERT as currently prescribed often results in supra-physiological levels of estrogens, with attendant unwanted side effects. Such high levels may be necessary for treatment of peri-menopausal symptoms (e.g., hot flashes) but perhaps not for prophylactic treatment of age-related cognitive decline. Moreover, post-menopausal women with an intact uterus are increasingly being advised for health reasons to take progesterone supplements with ERT. Therefore, it is important to understand possible interactions between estrogen and other hormones (progesterone, cortisol) in influencing cognition. The principal investigator is developing a long-term research program on ovarian steroids and the neurobiology of aging, with an initial focus on estrogen effects on cognition. The data collected will help guide the design of a planned ERT intervention study of healthy older women, by identifying appropriate estrogen target levels (i.e, associated with good cognition).